InterPro domain: IPR002880

This entry represents the N-terminal region of the pyruvate ferredoxin oxidoreductase, corresponding to the first two structural domains. This region is involved in inter subunit contacts [ 1 ]. Pyruvate oxidoreductase (POR) catalyses the final step in the fermentation of carbohydrates in anaerobic microorganisms [ 2 ]. This involves the oxidative decarboxylation of pyruvate with the participation of thiamine followed by the transfer of an acetyl moiety to coenzyme A for the synthesis of acetyl-CoA [ 3 ]. The family also includes pyruvate flavodoxin oxidoreductase as encoded by the nifJ gene in cyanobacterium which is required for growth on molecular nitrogen when iron is limited [ 3 ].

The PYR domain is found in many key metabolic enzymes which use TPP (also known as thiamine diphosphate) as a cofactor. TPP binds in the cleft formed by a PYR domain and a PP domain. The PYR domain, binds the aminopyrimidine ring of TPP, the PP domain binds the diphosphate residue. A polar interaction between the conserved glutamate of the PYR domain and the N1' of the TPP aminopyrimidine ring is shared by most TPP-dependent enzymes, and participates in the activation of TPP. The PYR and PP domains have a common fold, but do not share strong sequence conservation. The PP domain is not included in this entry. Most TPP-dependent enzymes have the PYR and PP domains on the same subunit although these domains can be alternatively arranged in the primary structure. TPP-dependent enzymes are multisubunit proteins, the smallest catalytic unit being a dimer-of-active sites. For many of these enzymes the active sites lie between PP and PYR domains on different subunits. However, for the homodimeric enzyme Desulfovibrio africanus pyruvate:ferredoxin oxidoreductase (PFOR), each active site lies at the interface of the PYR and PP domains from the same subunit [ 4 ].

This entry includes proteins characterized as pyruvate NADP+ oxidoreductase (PNO). PFOR and PNO catalyze the oxidative decarboxylation of pyruvate to form acetyl-CoA, a crucial step in many metabolic pathways. The facultative anaerobic mitochondrion of the photosynthetic protist Euglena gracilis oxidizes pyruvate with PNO [ 4 ]. IOR catalyzes the oxidative decarboxylation of arylpyruvates, such as indolepyruvate or phenylpyruvate.

1. Crystal structures of the key anaerobic enzyme pyruvate:ferredoxin oxidoreductase, free and in complex with pyruvate. Nat. Struct. Biol. 6, 182-90
2. Molecular and phylogenetic characterization of pyruvate and 2-ketoisovalerate ferredoxin oxidoreductases from Pyrococcus furiosus and pyruvate ferredoxin oxidoreductase from Thermotoga maritima. J. Bacteriol. 178, 248-57
3. Growth of the cyanobacterium Anabaena on molecular nitrogen: NifJ is required when iron is limited. Proc. Natl. Acad. Sci. U.S.A. 90, 8812-6
4. The origin of pyruvate: NADP+ oxidoreductase in mitochondria of Euglena gracilis. FEBS Lett 479, 155-6